This is an application for a K23 award for Dr. Virginia Sturm, a neuropsychology fellow at the University of California, San Francisco Memory and Aging Center (MAC). Dr. Sturm is establishing herself as a young investigator who conducts patient-oriented clinical research on emotion in neurodegenerative disease. This K23 will provide Dr. Sturm with the support necessary to accomplish the following goals: (1) to gain expertise in neurodegenerative disease, differential diagnosis, and behavioral neurology; (2) to advance her knowledge of psychophysiology by learning a new method, facial electromyography; (3) to become proficient in structural and functional neuroimaging analyses; (4) to obtain experience with clinical measures of real-world behavior; (5) to learn advanced statistical techniques; and (6) to develop an independent research career. To achieve these goals, Dr. Sturm has assembled a mentoring team that includes two primary mentors: Drs. Howard Rosen (a neurologist with expertise in neurodegenerative disease, psychophysiology, and structural neuroimaging) and William Seeley (a neurologist with expertise in neuropathology, functional neuroimaging, and resting state network connectivity analyses); two co-mentors: Drs. Bruce Miller (a neurologist with expertise in behavioral neurology, neurodegenerative disease, and clinical research) and Robert Levenson (a psychologist with expertise in psychophysiology, emotion, and empathy); and three consultants: Drs. James Gross (a psychologist with expertise in psychophysiology, facial electromyography, and emotion), John Neuhaus (a biostatistician with expertise in advanced multivariate statistical analyses), [and Gary Glover (an MRI physicist with technical expertise in functional magnetic resonance imaging methodologies)]. The proposed research project focuses on emotional empathy, an automatic affective reaction to others that occurs via physiological and behavioral mirroring mechanisms. Dr. Sturm will use laboratory-based measures of emotion to measure two forms of emotional empathy (i.e., facial mimicry and autonomic reactivity) in patients with behavioral variant frontotemporal dementia (bvFTD), patients with Alzheimer's disease (AD), and healthy control subjects (Aim 1). Dr. Sturm will integrate laboratory measures of emotional empathy with neuroimaging and clinical data in order to identify the neural systems that are related to emotional empathy impairment in bvFTD and preservation in AD (Aim 2) and to determine the real-world behavioral impact of emotional empathy deficits (Aim 3). Data collection will take place at the MAC and at the University of California, Berkeley. [By detailing specific, empathy-relevant, bvFTD-vulnerable neural network, these studies will inform disease models of bvFTD and suggest imaging biomarkers for measuring disease progression and treatment response. Dr. Sturm's K23 training will prepare her to conduct interdisciplinary studies of emotion in neurodegenerative disease and to conduct future studies that detail the neuroanatomical bases of emotional dysfunction in various clinical disorders.] PUBLIC HEALTH RELEVANCE: [A better understanding of the neuroanatomical system that underlies empathic dysfunction will be crucial for improving animal models of behavioral variant front temporal dementia and enhancing drug development efforts in humans by identifying the most relevant brain structures. This information may also improve disease models of other disorders in which socioemotional deficits are a central feature.]